The fibroblast growth factor (FGF) family is now known to consist of at least fourteen members, namely, FGF-1to FGF-10 and homologous factors FHF-1 to FHF-4.
FGF-1(aFGF) and FGF-2 (bFGF), which were originally isolated as mitogens for fibroblasts from the brain and the pituitary gland, are widely expressed in developing and adult tissues. These polypeptides exhibit multiple biological activities, including angiogenesis, mitogenesis, cellular differentiation and wound healing; see Baird et al., Cancer Cells, Volume 3, pages 239-243 (1991) and Burgess et al., Annual Review of Biochemistry, Volume 58, pages 575-606 (1989). FGF-3 (also known as "int-2"), FGF-4 (also known as "hst/kFGF"), FGF-5 and FGF-6 were each identified originally as oncogene products: see Dickson et al., Annual Review of the New York Academy of Sciences, Volume 683, pages 18-26 (1991); Yoshida et al., Annual Review of the New York Academy of Sciences, Volume 683, pages 27-37 (1991); Goldfarb et al., Annual Review of the New York Academy of Sciences, Volume 683, pages 38-52 (1991); and Coulier et al., Annual Review of the New York Academy of Sciences, Volume 683, pages 53-61 (1991). FGF-7 (also referred to as "KGF") was isolated as a mitogenic factor for cultured keratinocytes; see Aaronson et al., Annual Review of the New York Academy of Sciences, Volume 683, pages 62-77 (1991). FGF-8 and FGF-9 were isolated as an androgen-induced growth factor and a glial-activating factor from mouse mammary carcinoma cells and human glioma cells, respectively; see Tanaka et al., Proceedings of the National Academy of Sciences USA, Volume 89, pages 8928-8932 (1991) and Miyamoto et al., Molecular Cell Biology, Volume 13, pages 4251-4259 (1993). FGF-10 was identified from rat embryos by homology-based polymerase chain reaction (PCR); see Yamasaki et al., Journal of Biological Chemistry, Volume 271, pages 15918-15921 (1996). These FGFs are expressed predominantly during embryonic development and in some adult tissues.
The four homologous factors (or "FHFs") were identified from the human retina by a combination of random cDNA sequencing, searches of existing sequence data bases and homology-based poylmerase chain reactions; see Smallwood et al., Proceedings of the National Academy of Sciences USA, Volume 93, pages 9850-9857 (1996). These FHFs are expressed predominantly in the developing and mature nervous systems. It has been proposed that FHF-1, FHF-2, FHF-3 and FHF-4 should be designated as FGF-11, FGF-12, FGF-13 and FGF-14, respectively, in accordance with the recommendation of the Nomenclature Committee; see Coulier et al., Journal of Molecular Evolution, Volume 44, pages 43-56 (1997).